A central problem in cancer research is determining the functional organization of membranes in normal and tumor cells. The purpose of this project is to develop and apply a new kind of microscopy designed to examine differences in cell surfaces and other membranes. This imaging technique, photoelectron microscopy, utilizes the basic principle that all materials will photoemit electrons under the action of light of sufficient energy. The instrument can be thought of as an analogue of flourescence microscopy but with the much higher resolution of electron optics. The mechanism of contrast is different from transmission and scanning electron microscopy permitting the visualization of different biochemical structures (e.g. very fine cell surface detail, photoelectron labels and also aromatic chemical carcinogens). Recently, the University of Oregon photoelectron microscope funded by this grant from the National Cancer Institute has been upgraded from 500 Angstroms to 150 Angstroms resolution. The major goals for this renewal period take advantage of this improvement by shifting emphasis from model systems to cells in tissue culture. Studies on several cell lines including uncoated and unstained mouse 3T3 cells, SV40 transformed mouse 3T3 cells, chicken embryo fibroblasts and tumor cells (e.g. neuroblastoma cells). Scanning electron microscopy will be used as a control. New labeling methods will be explored and advantage will be taken of the high photoemissive yields of polycyclic aromatic chemical carcinogens such as benzo(a)pyrene to study their binding behavior to cellular macromolecules. Development of the microscope itself will continue in parallel with the biological studies.